Coating medication to effect a controlled or extended release administration profile is well known in the art. Drug manufacturers have been using such methods to provide oral administration of medications that enter the body over a predetermined, extended period of time.
Controlled release administration provides many benefits to a patient. For example, controlled release administration can reduce the number of times that a patient is required to self-administer medication, thus reduce the possibility that the patient will forget to take his or her medication during the day Analgesics and antipyretics, such as acetaminophen are often self-administered over the course of a day to help alleviate pain or fever from which a person is suffering. Often, such symptoms can last for long periods of time. However, the symptoms need not affect the person's typical daily routine. Thus, the person may not remember to take his or her medication because of other daily activities.
As a result, it has become advantageous to provide an extended or controlled release analgesic drug for self-administration. Such controlled release administration can substantially reduce the number of times that a patient takes medication during the day. The controlled release properties also facilitate night time administration in that a controlled release coating can be provided to sufficiently extend over the period during which the person is asleep.
In preparing and applying a controlled or extended release coating it is known to prepare the medication as a quantity of small pellets, non-pareils or prills, which are small, generally spherically shaped form of the medication. The prills are coated with, for example, an aqueous, ethyl-cellulose based film coating product, which dissolves when subjected to humidity or liquid aqueous media. The prills can be contained within a gelatin capsule or blister. The capsule, like the ethyl-cellulose coating, dissolves when subjected to humid conditions or liquid aqueous media. The blister is typically not administered to a patient, but rather is opened or separated and the contents emptied therefrom for use.
One method of applying the coating to the prills utilizes a technique referred to in the art as panning. This technique was originally developed for sugar-coating and is discussed by S. C. Porter in "Coating of Pharmaceutical Dosage Forms", Remington's Pharmaceutical Sciences, 18th ed., A. R. Gennaro ed., Chapter 90, Mack Publishing Co., Easton Pa. (1990) pages 1666-1675.
U.S. Pat. No. 4,820,522 teaches the preparation of a sustained release acetaminophen preparation that includes hydroxyethyl cellulose as an excipient and povidone (polyvinyl pyrrolidone) as a granulating agent to form a shaped and compressed medicament. The resulting compressed medicament is provided in the form of a compressed tablet or as a layer of a multilayered tablet. In this composition, the povidone, hydroxyethyl cellulose and other ingredients bind the acetaminophen in a sustained release solid matrix. A composition of this patent is stated to further require the inclusion of a "wicking agent" such as microcrystalline cellulose to wick fluids into the matrix and also an "erosion promoter" such as pregelatinized starch. Although a composition of this patent provides sustained release of acetaminophen to normal adults, such a composition is tableted and as such, cannot provide the medication to a patient who has difficulty swallowing a tablet.
Another method of applying the coating is to coat the prills in a fluidized bed coating system. One typical type of system is the Wurster-type coater. In such a system, the fluidized bed coating vessel includes a bottom air inlet nozzle and a top or upper air outlet nozzle. The vessel typically has a divergent middle body expansion section. At about the expansion section, an air distributor plate spans the vessel. The distributor plate defines an upper reactor section and a lower feed section or air inlet plenum. The distributor plate includes orifices therein to effect a relatively even air distribution across the plate.
A partition-like, cylindrical coating column extends upwardly from above the distributor plate into the reactor section. The space between the coating column and the vessel walls defines a downflow bed. The coating column is positioned above the distributor plate to define a gap therebetween. The gap is sized to permit the inflow of material from the downflow bed, through the gap, and into the column. A spray nozzle extends from the feed section into the coating column from below the distributor plate. The spray nozzle is configured to provide a spray of coating material into the column.
In operation, the vessel is charged with a quantity of prills to be coated. The prills rest in the downflow bed, above the distributor plate, and surrounding the coating column.
Air is supplied to the vessel through the air inlet nozzle, into the inlet plenum. The air flow rate is selected to fluidize the downflow bed. In a typical arrangement, the air flow is selected to establish an incipiently fluidized bed in the region surrounding the coating column. In the incipiently fluidized bed, the pressure drop across the bed is equal to the gravitational force acting on the prill particles. Thus, the bed is minimally fluidized, and no voids or channels are formed therein.
The coating material is fed into the coating column through the spray nozzle. The upward flow of material and air through the column creates a low pressure zone at the bottom thereof which draws the prills from the downflow bed, through the gap between the distributor plate and the column. As the prills enter the column, they are accelerated upwardly by the spray and air flow.
In the coating column and the space thereabove, intimate mixing of the prills and the coating material occurs. As the coated prills rise in the column and lose energy, they are forced outward, away from the upward flow stream above the column. When the prills lose sufficient energy to be overcome by gravitational forces, they fall back down onto the downflow bed. The process is continued until the entire batch of charged prills is coated. When the process is complete, the prills are removed from the vessel for further processing. In some fluidized bed coating systems, a significant amount of drying of the prills occurs within the reactor vessel upper areas prior to the prills falling back into the downflow column.
The particular process controls, flow rates and pressures are typically determined by, among other things, the particle size and density, the coating type and coating thickness desired, the conditions of the infed air, and the drying requirements. The particular process control parameters for a given system will be recognized by those skilled in the art.
Although the Wurster-type coater has been used to provide coatings of all types for the drug industry, it is desirable to be able to more closely predict the time release rates or the dissolution profiles of such coated medication. Due to the nature of the distributor plate arrangement, it has been observed that the prills can agglomerate at the coating column. The agglomeration of prills can result in uneven coating thereof, which in turn, can produce less predictable dissolution rates.
Accordingly, there continues to be a need for an extended release acetaminophen composition that can be used to treat children and adults who have difficulty swallowing tablets or capsules, and that exhibits a predictable profile for the extended release of the acetaminophen over a period of time.